Journal of Alzheimer's Disease - Volume 56, issue 3

Authors: Jaul, Efraim | Meiron, Oded

Article Type: Research Article

Abstract: The current theoretical investigation aimed to explore common pathophysiological mechanisms underlying dementia and pressure ulcers (PU). Along with the increased longevity, especially in frail elderly patients, there is a higher rate of functional and cognitive impairment with dementia coinciding with immobility, which results in a higher rate of PU. Understanding common etiological paths resulting in pressure ulcers and dementia is likely to produce new treatment strategies that could lead to the prevention of comorbid complications. Data collected from elderly dementia patients indicate a deterioration of several neurophysiological subsystems associated with motor, sensory, autonomic, cognitive, or behavioral pathways, supporting a “close …pathophysiological interrelation” perspective linking PU with dementia progression. Overall, the authors’ theoretical systemic-model of disease progression and PU comorbidity proposes that increased clinician awareness to PU in mild to moderate dementia may suppress the accelerated development of PU, resulting in less patient suffering, reduced long-term care hospitalization, and hopefully PU prevention. Show more

Keywords: Advanced dementia, Alzheimer’s disease, comorbidity, pressure ulcers

DOI: 10.3233/JAD-161134

Citation: Journal of Alzheimer's Disease, vol. 56, no. 3, pp. 861-866, 2017

Authors: Bastian, Frank O.

Article Type: Research Article

Abstract: The question whether Alzheimer’s disease is infectious as brought up in the recent editorial published in the Journal of Alzheimer ’s Disease is complicated by the controversy whether the causal agent is a microbe or a misfolded host protein (amyloid). The replicating amyloid (prion) theory, based upon data from studies of Creutzfeldt-Jakob disease (CJD) and other transmissible spongiform encephalopathies (TSEs), has been challenged since the prion can be separated from TSE infectivity, and spiroplasma, a wall-less bacterium, has been shown to be involved in the pathogenesis of CJD. Further support for a microbial cause for AD comes from occurrence …of mixed CJD/AD cases involving up to 15% of AD brains submitted to brain banks. The association of CJD with AD suggests a common etiology rather than simply being a medical curiosity. A co-infection with the transmissible agent of CJD, which we propose to be a Spiroplasma sp., would explain the diversity of bacteria shown to be associated with cases of AD. Show more

Keywords: Alzheimer’s disease, amyloid, bacteria, Creutzfeldt-Jakob disease, microbe, prion, spiroplasma, transmissible spongiform encephalopathy

DOI: 10.3233/JAD-160999

Citation: Journal of Alzheimer's Disease, vol. 56, no. 3, pp. 867-873, 2017

Authors: Wang, Hao | Hong, Xiaoyu | Wang, Yong

Article Type: Short Communication

Abstract: Mitochondrial dysfunction plays a pivotal role in Alzheimer’s disease (AD), even before signs of AD pathology are evident. Our previous research has shown that oxygen treatment can improve cognitive function in AD model mice. To address whether oxygen treatment is beneficial to mitochondrial biology, we analyzed differential expressions of hippocampal mitochondrial proteins in AD model mice given supplementary oxygen. Numerous respiratory chain, Kreb’s cycle, and glycolysis proteins were upregulated significantly after oxygen treatment, suggesting that oxygen therapy can alleviate mitochondrial damage. Furthermore, the treatment was associated with decreased expressions of some AD biomarkers, suggesting oxygen treatment to be a potential …therapy for AD. Show more

Keywords: Alzheimer’s disease, iTRAQ, mitochondria, oxidative phosphorylation, oxygen, proteomics

DOI: 10.3233/JAD-161010

Citation: Journal of Alzheimer's Disease, vol. 56, no. 3, pp. 875-883, 2017

Authors: Toombs, Jamie | Foiani, Martha S. | Paterson, Ross W. | Heslegrave, Amanda | Wray, Selina | Schott, Jonathan M. | Fox, Nick C. | Lunn, Michael P. | Blennow, Kaj | Zetterberg, Henrik

Article Type: Short Communication

Abstract: The effect of spinal manometers on cerebrospinal fluid (CSF) amyloid-β (Aβ) concentration was investigated. Pooled human CSF samples were divided in two, one half passed through a manometer into a collection tube, the other transferred directly to a collection tube. CSF was analyzed for Aβ38/40/42 using an electrochemiluminescence immunoassay. Relative to control, use of a manometer decreased Aβ38/40/42 concentration by 5.6% (±1.5SE), 4.4% (±1.7SE), and 4.3% (±2.4SE), respectively. The ratios of Aβ42 :40 , Aβ42 :38 , and Aβ40 :38 were not affected by manometer treatment. Factors which artificially lower CSF Aβ concentrations are relevant to clinical diagnosis for AD …and study design. Show more

Keywords: Alzheimer’s disease, amyloid-β, biomarkers, cerebrospinal fluid, manometer, pre-analytical factor

DOI: 10.3233/JAD-161126

Citation: Journal of Alzheimer's Disease, vol. 56, no. 3, pp. 885-891, 2017

Authors: Wu, Liyong | Liu, Jia | Sha, Longze | Wang, Xianling | Li, Jieying | Dong, Jing | Jia, Jianping

Article Type: Short Communication

Abstract: Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an autosomal dominant hereditary disease, featured by cerebral white matter degeneration with demyelination and axonal spheroids. We collected three gene-confirmed HDLS cases in our neurodegenerative clinic. Two HDLS cases were sporadic with novel mutations, while another case had a family history with previously described mutations. All three cases suffered memory problems with white matter lesions and pyramid signs. No obvious clinical differences were observed between sporadic and familial HDLS cases. Distinct features, such as subcortical calcification in brain computed tomography and asymmetric abnormal MRI signal along the pyramid tracts throughout brainstem and spinal …cord (cervical, thoracic, and lumbar segments), were observed in one sporadic case with novel mutation. Therefore, the interactions of genotype-phenotype still need to be further investigated. Show more

Keywords: Hereditary leukoencephalopathy with axonal spheroids (HDLS), novel mutation, pedigree, pyramid tract, sporadic case, subcortical calcification

DOI: 10.3233/JAD-161193

Citation: Journal of Alzheimer's Disease, vol. 56, no. 3, pp. 893-898, 2017

Authors: Innes, Kim E. | Selfe, Terry Kit | Khalsa, Dharma Singh | Kandati, Sahiti

Article Type: Research Article

Abstract: Background: While effective therapies for preventing or slowing cognitive decline in at-risk populations remain elusive, evidence suggests mind-body interventions may hold promise. Objectives: In this study, we assessed the effects of Kirtan Kriya meditation (KK) and music listening (ML) on cognitive outcomes in adults experiencing subjective cognitive decline (SCD), a strong predictor of Alzheimer’s disease. Methods: Sixty participants with SCD were randomized to a KK or ML program and asked to practice 12 minutes/day for 3 months, then at their discretion for the ensuing 3 months. At baseline, 3 months, and 6 months we measured …memory and cognitive functioning [Memory Functioning Questionnaire (MFQ), Trail-making Test (TMT-A/B), and Digit-Symbol Substitution Test (DSST)]. Results: The 6-month study was completed by 53 participants (88%). Participants performed an average of 93% (91% KK, 94% ML) of sessions in the first 3 months, and 71% (68% KK, 74% ML) during the 3-month, practice-optional, follow-up period. Both groups showed marked and significant improvements at 3 months in memory and cognitive performance (MFQ, DSST, TMT-A/B; p ’s≤0.04). At 6 months, overall gains were maintained or improved (p ’s≤0.006), with effect sizes ranging from medium (DSST, ML group) to large (DSST, KK group; TMT-A/B, MFQ). Changes were unrelated to treatment expectancies and did not differ by age, gender, baseline cognition scores, or other factors. Conclusions: Findings of this preliminary randomized controlled trial suggest practice of meditation or ML can significantly enhance both subjective memory function and objective cognitive performance in adults with SCD, and may offer promise for improving outcomes in this population. Show more

Keywords: Alzheimer’s disease, cognitive impairment, early memory loss, memory

DOI: 10.3233/JAD-160867

Citation: Journal of Alzheimer's Disease, vol. 56, no. 3, pp. 899-916, 2017

Authors: González-Muñoz, María José | Garcimartán, Alba | Meseguer, Isabel | Mateos-Vega, Carmen José | Orellana, José María | Peña-Fernández, Antonio | Benedí, Juana | Sánchez-Muniz, Francisco J.

Article Type: Research Article

Abstract: Background: Emerging evidence suggests that by affecting mineral balance, aluminum (Al) may enhance some events associated with neurodegenerative diseases. Aim: To examine the effect of Al(NO3 )3 exposure on brain Al, cooper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), silicon (Si), and zinc (Zn) levels, and the metal-change implication in brain oxidant and inflammatory status. Methods: Four groups of six-week-old male NMRI mice were treated for three months: i) controls, administrated with deionized water; ii) Al, which received Al(NO3 )3 ; iii) Al+silicic acid, which were given Al(NO3 )3 plus silicic acid; and …iv) Al+beer, which received Al(NO3 )3 plus beer. Results: Brain Al and TBARS levels and TNFα and GPx expressions increased, while Cu, Mn, and Zn levels, and catalase and CuZn-SOD expression decreased (at least, p  < 0.05) in Al versus control animals. Al, Si, and TBARS levels and TNFα expression decreased (p  < 0.05) in Al+silicic acid and Al+beer specimens while Cu, Mn, and Zn levels and antioxidant expression increased versus the Al group. Brain Al levels correlated negatively with those of Cu, Fe, Mn, and Zn, and catalase, CuZn-SOD, and GPx enzyme expressions but positively with Si and TBARS levels and TNFα expression. Two components of the principal component analysis (PCA) explained 71.2% of total data variance (p  < 0.001). PCA connected the pro-oxidant markers with brain Al content, while brain Zn and Cu levels were closer to antioxidant enzyme expression. Conclusion: Administration of Al(NO3 )3 induced metal imbalance, inflammation, and antioxidant status impairment in the brain. Those effects were blocked to a significant extent by silicic acid and beer administration. Show more

Keywords: Aluminum, aluminum nitrate, antioxidants, beer, brain, copper, enzyme expressions, iron, manganese, magnesium, silicic acid, Silicon, TBARS, TNFα , zinc

DOI: 10.3233/JAD-160972

Citation: Journal of Alzheimer's Disease, vol. 56, no. 3, pp. 917-927, 2017

Authors: Ismail, Zahinoor | Agüera-Ortiz, Luis | Brodaty, Henry | Cieslak, Alicja | Cummings, Jeffrey | Fischer, Corinne E. | Gauthier, Serge | Geda, Yonas E. | Herrmann, Nathan | Kanji, Jamila | Lanctôt, Krista L. | Miller, David S. | Mortby, Moyra E. | Onyike, Chiadi U. | Rosenberg, Paul B. | Smith, Eric E. | Smith, Gwenn S. | Sultzer, David L. | Lyketsos, Constantine | for the NPS Professional Interest Area of the International Society of to Advance Alzheimer’s Research and Treatment (NPS-PIA of ISTAART)

Article Type: Research Article

Abstract: Background: Mild behavioral impairment (MBI) is a construct that describes the emergence at ≥50 years of age of sustained and impactful neuropsychiatric symptoms (NPS), as a precursor to cognitive decline and dementia. MBI describes NPS of any severity, which are not captured by traditional psychiatric nosology, persist for at least 6 months, and occur in advance of or in concert with mild cognitive impairment. While the detection and description of MBI has been operationalized in the International Society to Advance Alzheimer’s Research and Treatment – Alzheimer’s Association (ISTAART-AA) research diagnostic criteria, there is no instrument that accurately reflects MBI …as described. Objective: To develop an instrument based on ISTAART-AA MBI criteria. Methods: Eighteen subject matter experts participated in development using a modified Delphi process. An iterative process ensured items reflected the five MBI domains of 1) decreased motivation; 2) emotional dysregulation; 3) impulse dyscontrol; 4) social inappropriateness; and 5) abnormal perception or thought content. Instrument language was developed a priori to pertain to non-demented functionally independent older adults. Results: We present the Mild Behavioral Impairment Checklist (MBI-C), a 34-item instrument, which can easily be completed by a patient, close informant, or clinician. Conclusion: The MBI-C provides the first measure specifically developed to assess the MBI construct as explicitly described in the criteria. Its utility lies in MBI case detection, and monitoring the emergence of MBI symptoms and domains over time. Studies are required to determine the prognostic value of MBI for dementia development, and for predicting different dementia subtypes. Show more

DOI: 10.3233/JAD-160979

Citation: Journal of Alzheimer's Disease, vol. 56, no. 3, pp. 929-938, 2017

Authors: Grill, Joshua D. | Holbrook, Andrew | Pierce, Aimee | Hoang, Dan | Gillen, Daniel L.

Article Type: Research Article

Abstract: Difficult participant recruitment is a consistent barrier to successful medical research. Potential participant registries represent an increasingly common intervention to overcome this barrier. A variety of models for registries exist, but few data are available to instruct their design and implementation. To provide such data, we surveyed 110 cognitively normal research participants enrolled in a longitudinal study of aging and dementia. Seventy-four (67%) individuals participated in the study. Most (78%, CI: 0.67, 0.87) participants were likely to enroll in a registry. Willingness to participate was reduced for registries that required enrollment through the Internet using a password (26%, CI: 0.16, …0.36) or through email (38%, CI: 0.27, 0.49). Respondents acknowledged their expectations that researchers share information about their health and risk for disease and their concerns that their data could be shared with for-profit companies. We found no difference in respondent preferences for registries that shared contact information with researchers, compared to honest broker models that take extra precautions to protect registrant confidentiality (28% versus 30%; p  = 0.46). Compared to those preferring a shared information model, respondents who preferred the honest broker model or who lacked model preference voiced increased concerns about sharing registrant data, especially with for-profit organizations. These results suggest that the design of potential participant registries may impact the population enrolled, and hence the population that will eventually be enrolled in clinical studies. Investigators operating registries may need to offer particular assurances about data security to maximize registry enrollment but also must carefully manage participant expectations. Show more

Keywords: Clinical trial, recruitment, registries

DOI: 10.3233/JAD-160873

Citation: Journal of Alzheimer's Disease, vol. 56, no. 3, pp. 939-946, 2017

Authors: Sundermann, Erin E. | Biegon, Anat | Rubin, Leah H. | Lipton, Richard B. | Landau, Susan | Maki, Pauline M. | for the Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: There is a growing recognition of sex differences in Alzheimer’s disease (AD). Females show an advantage over males on tests of verbal memory, which are used to diagnose AD and its precursor, amnestic mild cognitive impairment (aMCI). Women retain this advantage in aMCI despite reduced hippocampal volume and temporal lobe glucose metabolism. Here we examined whether this female advantage endures despite evidence of AD-specific pathology, cortical amyloid-β (Aβ) deposition measured with [18 F]AV45 (florbetapir) positron emission tomography. Participants with normal cognition (N = 304), aMCI (N = 515), and AD dementia (N = 175) were drawn from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Across and within …diagnostic groups, we conducted linear regressions to examine the interaction of sex with cortical Aβ burden on immediate and delayed recall on the Rey Auditory Verbal Learning Test (RAVLT) adjusting for age, education, and APOE4. In the overall group, sex by cortical Aβ interaction was significant for delayed recall only. Overall, delayed recall performance was significantly better in women versus men among those with low to moderate Aβ burden, but women and men performed similarly among those with high Aβ burden. In diagnosis-stratified analyses, a significant sex by cortical Aβ interaction was observed for delayed recall in the aMCI group, but not in the normal or AD dementia groups. Thus, women maintain a verbal memory advantage over men in aMCI despite similar levels of AD pathology. Although this advantage may benefit women by delaying verbal memory impairment until more advanced pathology, it may also delay diagnosis of aMCI and treatment intervention. Show more

Keywords: Amyloid, cognitive reserve, memory, positron-emission tomography, sex

DOI: 10.3233/JAD-160716

Citation: Journal of Alzheimer's Disease, vol. 56, no. 3, pp. 947-957, 2017